Digital Commons Network^™

Disclosing Disabilities: Barriers For Medical School Applicants, Sarah Leah Solomon, Aitan E. Magence, Harry Haran, Fern R. Juster, Kristina H. Petersen

2020-Current year OA Pubs

This study investigated the availability of accommodation request procedures for medical school admissions interviews and the accessibility of Technical Standards (TS) for candidates with disabilities (CWD) across Liaison Committee on Medical Education (LCME)-accredited institutions in the United States and Canada. Utilizing a cross-sectional study methodology, surveys were distributed to Deans of Admissions and Disabilities Resource Professionals (DRP) at all LCME-accredited US and Canadian MD programs. Surveys gathered data about interview formats, interview accommodation procedures, and TS accessibility during the 2018-2019 academic year. We received responses from 71 institutions (41.3%), with 56.3% survey completion rate (n = 40). Among respondents, interview …

Efficacy And Safety Of Dostarlimab In Combination With Chemotherapy In Patients With Dmmr/Msi-H Primary Advanced Or Recurrent Endometrial Cancer In A Phase 3, Randomized, Placebo-Controlled Trial (Engot-En6-Nsgo/Gog-3031/Ruby), Matthew A Powell, Carolyn Mccourt, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial.

METHODS: Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years. In the dMMR/MSI-H population of RUBY Part 1, analysis of progression-free survival by investigator assessment compared with …

Early Changes In Spatiotemporal Dynamics Of Remapped Circuits And Global Networks Predict Functional Recovery After Stroke In Mice, Ryan M Bowen, Jake Lee, Brendon Wang, Keith R Lohse, Hanyang Miao, Jonah A Padawer-Curry, Asher J Albertson, Eric C Landsness, Adam Q Bauer, Jin-Moo Lee

2020-Current year OA Pubs

SIGNIFICANCE: Stroke is the leading cause of chronic disability in the United States. How stroke size affects post-stroke repair and recovery is poorly understood.

AIM: We aim to investigate the effects of stroke size on early repair patterns and determine how early changes in neuronal circuits and networks predict functional outcomes after stroke.

APPROACH: We used wide-field optical imaging, photothrombosis, and the cylinder-rearing assay to examine changes in neuronal circuit and network activity in the context of functional recovery after stroke.

RESULTS: Larger strokes ablating

CONCLUSIONS: These results suggest that diffuse patterns of remapping, and desynchronization and hyperconnectivity of cortical …

Piezo1-Mediated Calcium Influx Transiently Alters Nuclear Mechanical Properties Via Actin Remodeling In Chondrocytes, Jaquelin M Garcia-Castorena, Rosa Riester, Miranda Gamino-Ornelas, Nikitha Ada, Farshid Guilak, Marina Danalache

2020-Current year OA Pubs

Mechanosensation allows cells to generate intracellular signals in response to mechanical cues from their environment. Previous research has demonstrated that mechanical stress can alter the mechanical properties of the nucleus, affecting gene transcription, chromatin methylation, and nuclear mechanoprotection during mechanical loading. PIEZO1, a mechanically gated Ca

De Novo Lipid Synthesis In Cardiovascular Tissue And Disease, Tariq J Khan, Clay F Semenkovich, Mohamed A Zayed

2020-Current year OA Pubs

Most tissues have the capacity for endogenous lipid synthesis. A crucial foundational pathway for lipid synthesis is de novo lipid synthesis (DNL), a ubiquitous and complex metabolic process that occurs at high levels in the liver, adipose and brain tissue. Under normal physiological conditions, DNL is vital in converting excess carbohydrates into fatty acids. DNL is linked to other pathways, including the endogenous synthesis of phospholipids and sphingolipids. However, abnormal lipid synthesis can contribute to various pathologies and clinical conditions. Experimental studies involving dietary restriction and in vivo genetic modifications provide compelling evidence demonstrating the significance of lipid synthesis in …

Expert Consensus On The Diagnosis And Management Of Digoxin Toxicity, Jason B Hack, Sue Wingate, Ron Zolty, Michael W Rich, Paul J Hauptman

2020-Current year OA Pubs

While there has been a decline in the use of digoxin in patients with heart failure and atrial fibrillation, acute and chronic digoxin toxicity remains a significant clinical problem. Digoxin's narrow therapeutic window and nonspecific signs and symptoms of toxicity create clinical challenges and uncertainty around the diagnostic criteria of toxicity and responsive treatment choices for the bedside clinician. A systematic review of published literature on digoxin toxicity (34,587 publications over 6 decades, with 114 meeting inclusion criteria) was performed to develop 33 consensus statements on diagnostic and therapeutic approaches which were then evaluated through a modified Delphi process involving …

Nutcracker Syndrome (A Delphi Consensus), Floor Heilijgers, Suresh Vedantham, Et Al.

2020-Current year OA Pubs

BACKGROUND: Nutcracker syndrome (NCS) describes the symptomatic compression of the left renal vein between the aorta and superior mesenteric artery. Whereas asymptomatic compression is a common radiological finding, patients with NCS can report a range of symptoms. There are no specific diagnostic criteria and interventions include a range of open surgical and endovascular procedures. Therefore, we wished to develop an international consensus document covering aspects of diagnosis, management, and follow-up for patients with NCS.

METHODS: A three-stage modified Delphi consensus was performed. A steering committee developed 37 statements covering 3 categories for patients with NCS: diagnosis, management, and follow-up. These …

Validating A Novel Measure For Assessing Patient Openness And Concerns About Using Artificial Intelligence In Healthcare, Bryan A Sisk, Alison L Antes, Sunny C Lin, Paige Nong, James M Dubois

2020-Current year OA Pubs

OBJECTIVES: Patient engagement is critical for the effective development and use of artificial intelligence (AI)-enabled tools in learning health systems (LHSs). We adapted a previously validated measure from pediatrics to assess adults' openness and concerns about the use of AI in their healthcare.

STUDY DESIGN: Cross-sectional survey.

METHODS: We adapted the 33-item "Attitudes toward Artificial Intelligence in Healthcare for Parents" measure for administration to adults in the general US population (AAIH-A), recruiting participants through Amazon's Mechanical Turk (MTurk) crowdsourcing platform. AAIH-A assesses openness to AI-driven technologies and includes 7 subscales assessing participants' openness and concerns about these technologies. The openness …

Head-To-Head Preclinical Treatment Design Prioritizes Promising Therapies For Neurofibromatosis Type 1 Optic Glioma Clinical Translation, Talia Eligator, Jit Chatterjee, Shintaro Yamada, Anthony Kirchner, Hareesh B Nair, Jason R Fangusaro, David H Gutmann

2020-Current year OA Pubs

BACKGROUND: Authenticated preclinical brain tumor models provide unprecedented opportunities to evaluate next-generation treatments. However, some therapies with robust anti-tumor activity in mice fail in human trials, highlighting the need to better prioritize candidates for clinical translation. Herein, we implemented a head-to-head preclinical strategy using a well-characterized murine model of NF1-optic pathway glioma (

METHODS:

RESULTS: While all agents restored normal tissue architecture, reduced ON proliferation, and decreased TME soluble mediator and tumor cell marker RNA expression, only lamotrigine and mirdametinib also reduced ON volume. Everolimus, lamotrigine, and HBS-101 restored RNFL thickness to wild-type levels, whereas carboplatin showed a trend towards …

Barriers And Facilitators To Implementing A Single-Visit, Screen-And-Treat Approach With Thermal Ablation For Cervical Cancer Prevention In Kenya, Harriet Fridah Adhiambo, Thomas Odeny, Et Al.

2020-Current year OA Pubs

Cervical cancer continues to be a major global threat to women's health, with approximately 660,000 women diagnosed annually, 94% of whom are in low- and middle-income countries (LMICs). The high disease burden in LMICs is partly due to suboptimal adoption and widespread implementation of effective preventive interventions. This study explored drivers of implementation success and failure for a future single-visit, screen, and treat approach with thermal ablation (SV-SAT + TA), referred to as TIBA in Kenya. Guided by the Consolidated Framework for Implementation Research (CFIR framework), we conducted in-depth interviews with 34 participants (frontline health workers, health facility managers, and …

Structural Diversity Of Axonemes Across Mammalian Motile Cilia, Miguel Ricardo Leung, Chen Sun, Jianwei Zeng, Jacob R Anderson, Qingwei Niu, Wei Huang, Willem E M Noteborn, Alan Brown, Tzviya Zeev-Ben-Mordehai, Rui Zhang

2020-Current year OA Pubs

Reproduction, development and homeostasis depend on motile cilia, whose rhythmic beating is powered by a microtubule-based molecular machine called the axoneme. Although an atomic model of the axoneme is available for the alga Chlamydomonas reinhardtii

Enhancing Engagement In Hiv Care Among Adolescents And Young Adults: A Focus On Phone-Based Navigation And Relationship Building To Address Barriers In Hiv Care, Harriet Fridah Adhiambo, Dorothy Imbuka Mangale, Elvin Geng, Et Al.

2020-Current year OA Pubs

Structural, psychological, and clinical barriers to HIV care engagement among adolescents and young adults living with HIV (AYAH) persist globally despite gains in HIV epidemic control. Phone-based peer navigation may provide critical peer support, increase delivery flexibility, and require fewer resources. Prior studies show that phone-based navigation and automated text messaging interventions improve HIV care engagement, adherence, and retention among AYAH. However, little is known about AYAH experiences utilizing electronic phone-based peer navigation and automated text messaging (E-NAV). We assessed the experiences of AYAH receiving phone-based peer navigation to address barriers to HIV care engagement and viral suppression. We purposefully …

Nanobody Screening And Machine Learning Guided Identification Of Cross-Variant Anti-Sars-Cov-2 Neutralizing Heavy-Chain Only Antibodies, Peter R. Mcilroy, Zhuoming Liu, Sean Whelan, Et Al.

2020-Current year OA Pubs

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to persist, demonstrating the risks posed by emerging infectious diseases to national security, public health, and the economy. Development of new vaccines and antibodies for emerging viral threats requires substantial resources and time, and traditional development platforms for vaccines and antibodies are often too slow to combat continuously evolving immunological escape variants, reducing their efficacy over time. Previously, we designed a next-generation synthetic humanized nanobody (Nb) phage display library and demonstrated that this library could be used to rapidly identify highly specific and potent neutralizing heavy chain-only antibodies (HCAbs) with prophylactic and …

Patient Stratification By Genetic Risk In Alzheimer's Disease Is Only Effective In The Presence Of Phenotypic Heterogeneity, Jack Euesden, Muhammad Ali, Chloe Robins, Praveen Surendran, Padhraig Gormley, Alzheimer’S Disease Neuroimaging Initiative, David Pulford, Carlos Cruchaga

2020-Current year OA Pubs

Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science. In four cohorts (n = 7241), we performed genome-wide association studies (GWAS) and Mendelian randomization (MR) to discover novel targets associated with progression and assess causal relationships. We tested opportunities for patient stratification by deriving …

What Is The Optimal Management Of Metastatic Spine Patients With Intermediate Spinal Instability Neoplastic Scores: To Operate Or Not To Operate?, William Chu Kwan, Matthew L Goodwin, Et Al.

2020-Current year OA Pubs

STUDY DESIGN: Systematic review.

OBJECTIVE: In patients with extradural metastatic spine disease, we sought to systematically review the outcomes and complications of patients with intermediate Spinal Instability Neoplastic Score (SINS) lesions undergoing radiation therapy, percutaneous interventions, minimally invasive surgeries, or open spinal surgeries.

METHODS: Following PRISMA guidelines for systematic reviews, MEDLINE, EMBASE, Web of Science, the Cochrane Database of Systematic Reviews and the Cochrane Center Register of Controlled Trials were queried for studies that reported on SINS intermediate patients who underwent: 1) radiotherapy, 2) percutaneous intervention, 3) minimally invasive, or 4) open surgery. Dates of publication were between 2013-22. Patients …

Liquid Biopsy For Spinal Tumors: On The Frontiers Of Clinical Application, Sze Kiat Tan, Matthew L Goodwin, Et Al.

2020-Current year OA Pubs

STUDY DESIGN: Narrative review.

OBJECTIVES: This article aims to provide a narrative review of the current state of research for liquid biopsy in spinal tumors and to discuss the potential application of liquid biopsy in the clinical management of patients with spinal tumors.

METHODS: A comprehensive review of the literature was performed using PubMed, Google Scholar, Medline, Embase and Cochrane databases, and the review was limited to articles of English language. All the relevant articles which were identified to be related to liquid biomarker study in spinal tumors, were studied in full text.

RESULTS: Liquid biopsy has revolutionized the field …

Prevention And Management Of Posterior Wound Complications Following Oncologic Spine Surgery: Narrative Review Of Available Evidence And Proposed Clinical Decision-Making Algorithm, Owen P Leary, Matthew L Goodwin, Et Al.

2020-Current year OA Pubs

STUDY DESIGN: Narrative Review.

OBJECTIVE: Contextualized by a narrative review of recent literature, we propose a wound complication prevention and management algorithm for spinal oncology patients. We highlight available strategies and motivate future research to identify optimal and individualized wound management for this population.

METHODS: We conducted a search of recent studies (2010-2022) using relevant keywords to identify primary literature in support of current strategies for wound complication prevention and management following spine tumor surgery. When primary literature specific to spine tumor cases was not available, data were extrapolated from studies of other spine surgery populations. Results were compiled into …

Aav Gene Therapy For Duchenne Muscular Dystrophy: The Embark Phase 3 Randomized Trial, Jerry R Mendell, Craig M Zaidman, Et Al.

2020-Current year OA Pubs

Duchenne muscular dystrophy (DMD) is a rare, X-linked neuromuscular disease caused by pathogenic variants in the DMD gene that result in the absence of functional dystrophin, beginning at birth and leading to progressive impaired motor function, loss of ambulation and life-threatening cardiorespiratory complications. Delandistrogene moxeparvovec, an adeno-associated rh74-viral vector-based gene therapy, addresses absent functional dystrophin in DMD. Here the phase 3 EMBARK study aimed to assess the efficacy and safety of delandistrogene moxeparvovec in patients with DMD. Ambulatory males with DMD, ≥4 years to <8 years of age, were randomized and stratified by age group and North Star Ambulatory Assessment (NSAA) score to single-administration intravenous delandistrogene moxeparvovec (1.33 × 10

Cancer-Targeted Pro-Theranostic Bi-Metallic Organo-Coordination Nanoparticles, Hengbo Huang, Lei Fang, Janaka Wansapura, Julie L Prior, Brad Manion, Baogang Xu, Cody Hongsermeier, Nisha Gamadia, Nicole Blasi, Rui Tang, Christopher Egbulefu, Monica Shokeen, James D Quirk, Samuel Achilefu

2020-Current year OA Pubs

No abstract provided.

Social Anxiety, Negative Affect, And Hearing Difficulties In Adults, Katrina Kate S. Mcclannahan, Sarah Mcconkey, Julia M Levitan, Thomas L Rodebaugh, Jonathan E Peelle

2020-Current year OA Pubs

Subjective ratings of communication function reflect both auditory sensitivity and the situational, social, and emotional consequences of communication difficulties. Listeners interact with people and their environment differently, have various ways of handling stressful situations, and have diverse communication needs. Therefore, understanding the relationship between auditory and mental health factors is crucial for the holistic diagnosis and treatment of communication difficulty, particularly as mental health and communication function may have bidirectional effects. The goal of this study was to evaluate the degree to which social anxiety and negative affect (encompassing generalized anxiety, depression, and anger) contributed to subjective communication function (hearing …

Cause Of Death For Heart Transplant Patients, An Autopsy Study, Justin Burk, Cory T Bernadt, Jon Ritter, Chieh-Yu Lin

2020-Current year OA Pubs

INTRODUCTION: Heart transplantations are lifesaving for patients with end-stage heart failure. It is pertinent for the multidisciplinary care team to understand how heart transplant patients succumbed to death and the complications that occurred. In this study, we performed a comprehensive retrospective review of all the autopsies performed in our institute for heart transplant patients and report the trend of demographic data, cause of death, and autopsy findings.

MATERIALS AND METHODS: Reports, photos, and slides of autopsies performed at our institute from 1990 to 2023 for heart transplant patients were reviewed. Pertinent demographic data (age, gender, pretransplant diagnosis), clinical data (clinical …

Revisiting Abdominal Wall "Morbidity" Of The Extensile Anterolateral Approach To The Thoracolumbar Spine, Alekos A Theologis, Andrew P Collins, Kanwar Parhar, Munish C Gupta

2020-Current year OA Pubs

PURPOSE: To assess patients' perceptions of their abdominal wall following extensile anterolateral approaches to the thoracolumbar spine for adult spinal deformity (ASD) using validated questionnaires.

METHODS: Adults who underwent anterior-posterior thoracolumbar spinal operations to the pelvis for ASD in which the anterior fusion was performed through an extensile anterolateral approach were reviewed. Three questionnaires were administered at least 1 year following surgery and included The Abdominal Core Health Quality Collaborative Survey (AHS-QC), The Patient Scar Assessment Scale (PSAS), and The Anterior Abdominal Incision Questionnaire (AAIQ).

RESULTS: Fifty-one patients (80.4% female, median age 65 years) were included. Average follow-up was 2.8 …

Whole Genome Sequence Analysis Of Low-Density Lipoprotein Cholesterol Across 246 K Individuals, Margaret Sunitha Selvaraj, Lisa De Las Fuentes, Susan K. Dutcher, Et Al.

2020-Current year OA Pubs

No abstract provided.

Domain Mapping Of Disease Mutations Reveals Pathogenic Sorl1 Variants In Alzheimer's Disease, Olav M. Andersen, Carlos Cruchaga, Maria Victoria Fernandez, Et Al.

2020-Current year OA Pubs

No abstract provided.

Effects Of Obesity On Plasma Biomarker And Amyloid Pet Trajectories In Alzheimer's Disease, Soheil Mohammadi, Farzaneh Rahmani, Mahsa Dolatshahi, Suzanne E Schindler, Cyrus A Raji, Adni Collaborators

2020-Current year OA Pubs

INTRODUCTION: Obesity is a risk factor for Alzheimer's disease (AD), but its impact on AD blood biomarker (BBM) and amyloid positron emission tomography (PET) trajectories is unknown.

METHODS: One thousand two hundred twenty-eight plasma samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were assessed using six leading commercial tests (C2N, Fujirebio, Janssen, ALZpath, Roche, and Quanterix). Amyloid PET scans were used to assess amyloid burden in Centiloids (CLs). Spearman partial correlations assessed cross-sectional associations, while linear mixed-effects models examined the longitudinal impact of obesity status on BBMs and CLs.

RESULTS: Higher body mass index at baseline was correlated with lower …

Assessing The Clinical Meaningfulness Of Slowing Cdr-Sb Progression With Disease-Modifying Therapies For Alzheimer's Disease, Sarah M Hartz, Suzanne E Schindler, Marissa L Streitz, Krista L Moulder, Jessica Mozersky, Guoqiao Wang, Chengjie Xiong, John C Morris

2020-Current year OA Pubs

INTRODUCTION: For many patients and caregivers, a major goal of disease-modifying treatments (DMTs) for Alzheimer's disease (AD) dementia is to extend independence in instrumental and basic activities of daily living (IADLs and BADLs). The goal of this study was to estimate the effect of treatments on the time remaining independent in IADLs and BADLs.

METHODS: Participants at the Knight Alzheimer Disease Research Center (Knight ADRC) who met eligibility criteria for recent DMT trials were studied: age ≥60 years at baseline, clinical diagnosis of very mild or mild AD dementia (global Clinical Dementia Rating [CDR] score 0.5 or 1), biomarker confirmation …

Schistosomiasis Interventions In Africa: Assessment And Systematic Review, Christopher Yaw Dumevi, George Boateng Kyei, Patience B Tetteh-Quarcoo, James-Paul Kretchy, Irene Ayi, Patrick F Ayeh-Kumi

2020-Current year OA Pubs

No abstract provided.

Qualitative And Quantitative Analysis Of A Novel Dental Health Education Program To Improve Dental Care Utilization By Bhutanese-, Burmese-, And Swahili-Speaking Refugees In A Midwestern United States City, Chandra Swanson, Katherine Gordon, Kelly Kreisler, Elizabeth Montgomery Collins

2020-Current year OA Pubs

No abstract provided.

Estimating Preclinical Amyloid Positivity: A Case Study Transporting Adni To Aric, Emma K Stapp, Elizabeth Rose Mayeda, Elizabeth A Stuart, Rebecca F Gottesman, Scott C Zimmerman, Dean F Wong, Thomas H Mosley, Michael E Griswold, M Maria Glymour, Melinda C Power, Alzheimer's Disease Neuroimaging Initiative

2020-Current year OA Pubs

INTRODUCTION: Alzheimer's disease and related dementias researchers have benefited from deeply phenotyped clinical samples; however, there is a critical need for estimates that generalize to diverse, representative populations. Use of a statistical approach from causal inference, "transport," may allow generalization of findings from clinical samples to other target populations. Here we explore the feasibility and validity of extending results from a clinical sample, the Alzheimer's Disease Neuroimaging Initiative (ADNI), to a community-based target sample, the Atherosclerosis Risk in Communities Study Positron Emission Tomography Amyloid Imaging Study (ARIC-PET) using transport estimation and a standard approach, direct standardization, which itself can be …

Impact Of Genetic Counseling And Testing In Individuals At High Risk Of Familial Alzheimer's Disease From Latin America: A Non-Randomized Controlled Trial, Pablo M Bagnati, Ellen Ziegemeier, Eric Mcdade, Randall J Bateman, Jorge J Llibre-Guerra, Et Al.

2020-Current year OA Pubs

INTRODUCTION: This study involved evaluating a tailored genetic counseling and testing (GCT) protocol for families at risk of autosomal dominant Alzheimer's disease (ADAD) in Latin America (LatAm), focusing on essential cultural and regional adaptations.

METHODS: We conducted a non-randomized controlled trial among ADAD families in Colombia and Argentina. Participants were categorized based on their decision to learn their genetic status (GS), with further comparisons between mutation-positive versus mutation-negative participants who learned their status. Psychological impacts were measured using validated scales for anxiety and depression.

RESULTS: Of the 122 eligible participants, 97 completed the GCT protocol, and 87 opted to learn …